scholarly journals Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells

2005 ◽  
Vol 202 (6) ◽  
pp. 783-791 ◽  
Author(s):  
Götz R.A. Ehrhardt ◽  
Joyce T. Hsu ◽  
Lanier Gartland ◽  
Chuen-Miin Leu ◽  
Shuangyin Zhang ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
Chemokine Receptors ◽  
Cell Activation ◽  
Somatic Hypermutation ◽  
Cell Receptor ◽  
Memory B Cells ◽  
Cell Surface Expression ◽  
Lymphoid Tissues ◽  
Activation Markers

The FcRH4 transmembrane molecule, a member of the Fc receptor homologue family, can potently inhibit B cell receptor (BCR) signaling. We show that cell surface expression of this immunoregulatory molecule is restricted to a subpopulation of memory B cells, most of which lack the classical CD27 marker for memory B cells in humans. The FcRH4+ and FcRH4− memory B cells have undergone comparable levels of immunoglobulin isotype switching and somatic hypermutation, while neither subpopulation expresses the transcription factors involved in plasma cell differentiation. The FcRH4+ memory cells are morphologically distinctive large lymphocytes that express the CD69, CD80, and CD86 cell activation markers. They are also shown to be poised to secrete high levels of immunoglobulins in response to stimulation with T cell cytokines, but they fail to proliferate in response either to BCR ligation or Staphylococcus aureus stimulation. A heightened expression of the CCR1 and CCR5 chemokine receptors may facilitate their preferential localization in lymphoid tissues near epithelial surfaces. Cell surface FcRH4 expression thus marks a unique population of memory B cells with distinctive morphology, functional capabilities, and tissue localization.

scholarly journals P063 B-cell receptor signalling in lymphoid tissues may be regulated by CEACAM1

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S166-S166
Author(s):  
T Nagaishi ◽  
N Tsugawa ◽  
D Yamada ◽  
T Watabe ◽  
M Onizawa ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphoid Tissues ◽  
B Cell Activation ◽  
Activation Markers

Abstract Background It has been recently shown that the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) expressed in T cells may regulate immune responses in the gut. Moreover, it has also been reported that the treatments with either an agonistic monoclonal antibody (mAb) or natural ligands for this molecule can suppress colitis severity in murine models of inflammatory bowel diseases (IBD). On the other hand, in addition to T cells, B cells are also an important population in the gut-associated lymphoid tissues (GALT) that orchestrate mucosal homeostasis. However, the role of CEACAM1 in B cells has not been elucidated. Methods We analysed primary B-cell subsets in the lymphoid tissues of wild-type C57BL6 mice as well as a murine B-cell line, A20, to determine the expressions and functions of CEACAM1. Results FACS analysis of the lymphocyte subsets isolated from secondary lymphoid tissues such as spleen, mesenteric lymph nodes and Peyer’s patches of C57BL6 revealed higher expression level of CEACAM1 on B-cell surface than that of T cells. Bone marrow analysis showed that such CEACAM1 expression was increased during maturation and differentiation process of B cells. When isolated splenic B cells were stimulated with LPS, anti-CD40 or anti-μ chain Abs in the presence of agonistic anti-CEACAM1 mAb, the usual increased cytokine productions (such as IL-4 and IL-5 by activation via B cell receptor (BCR) signalling) were specifically suppressed by CEACAM1 signalling rather than B-cell activations via either TLR4 or CD40 signalling. Immunofluorescent studies using confocal microscopy revealed co-localisation of CEACAM1 and BCR when B cells were activated with anti-μ chain Ab. Given these results, A20 cells were transfected with CEACAM1 cDNA. Biochemical analysis showed that an inducible overexpression of CEACAM1 suppressed the BCR signalling in these cells when compared with that of vector alone-transfected control. Moreover, the overexpression of CEACAM1 in these cells resulted in reduced expressions of activation markers such as CD69, CD80, CD86, MHC-I and -II on the cell surface. These observations were associated with decreased Ca2+ influx and suppressed cytokine production by the overexpression of CEACAM1 after BCR signal activation. Conclusion These results suggest that CEACAM1 can regulate B-cell activation and differentiation specifically via BCR signalling in the lymphoid tissues. Therefore, this molecule can be a therapeutic target in IBD by regulating of both T-cell and B-cell activation in GALT.

scholarly journals Carbohydrate-dependent B cell activation by fucose-binding bacterial lectins

2019 ◽  
Vol 12 (571) ◽  
pp. eaao7194 ◽  
Author(s):  
Isabel Wilhelm ◽  
Ella Levit-Zerdoun ◽  
Johanna Jakob ◽  
Sarah Villringer ◽  
Marco Frensch ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
B Cell Activation ◽  
Intracellular Ca ◽  
Bacterial Lectins

Bacterial lectins are typically multivalent and bind noncovalently to specific carbohydrates on host tissues to facilitate bacterial adhesion. Here, we analyzed the effects of two fucose-binding lectins, BambL fromBurkholderia ambifariaand LecB fromPseudomonas aeruginosa, on specific signaling pathways in B cells. We found that these bacterial lectins induced B cell activation, which, in vitro, was dependent on the cell surface expression of the B cell antigen receptor (BCR) and its co-receptor CD19, as well as on spleen tyrosine kinase (Syk) activity. The resulting release of intracellular Ca2+was followed by an increase in the cell surface abundance of the activation marker CD86, augmented cytokine secretion, and subsequent cell death, replicating all of the events that are observed in vitro upon canonical and antigen-mediated B cell activation. Moreover, injection of BambL in mice resulted in a substantial, BCR-independent loss of B cells in the bone marrow with simultaneous, transient enlargement of the spleen (splenomegaly), as well as an increase in the numbers of splenic B cells and myeloid cells. Together, these data suggest that bacterial lectins can initiate polyclonal activation of B cells through their sole capacity to bind to fucose.

scholarly journals Selective dysregulation of the FcγIIB receptor on memory B cells in SLE

2006 ◽  
Vol 203 (9) ◽  
pp. 2157-2164 ◽  
Author(s):  
Meggan Mackay ◽  
Anfisa Stanevsky ◽  
Tao Wang ◽  
Cynthia Aranow ◽  
Margaret Li ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Cell Receptor ◽  
Memory B Cells ◽  
Therapeutic Interventions ◽  
B Cell Activation ◽  
Loss Of Self ◽  
Novel Target

The inappropriate expansion and activation of autoreactive memory B cells and plasmablasts contributes to loss of self-tolerance in systemic lupus erythematosus (SLE). Defects in the inhibitory Fc receptor, FcγRIIB, have been shown to contribute to B cell activation and autoimmunity in several mouse models of SLE. In this paper, we demonstrate that expression of FcγRIIB is routinely up-regulated on memory B cells in the peripheral blood of healthy controls, whereas up-regulation of FcγRIIB is considerably decreased in memory B cells of SLE patients. This directly correlates with decreased FcγRIIB-mediated suppression of B cell receptor–induced calcium (Ca2+) response in those B cells. We also found substantial overrepresentation of African-American patients among those who failed to up-regulate FcγRIIB. These results suggest that the inhibitory receptor, FcγRIIB, may be impaired at a critical checkpoint in SLE in the regulation of memory B cells; thus, FcγRIIB represents a novel target for therapeutic interventions in this disease.

scholarly journals Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells.

1983 ◽  
Vol 158 (2) ◽  
pp. 265-279 ◽  
Author(s):  
K Bottomly ◽  
B Jones ◽  
J Kaye ◽  
F Jones
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Cell Surface Expression ◽  
Th Cells ◽  
Th Cell ◽  
Ia Antigens

We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines. The cloned Th cells are antigen specific, in this case ovalbumin (OVA), self-Ia recognizing, and induce antibody secretion only if the hapten, PC, is physically linked to the carrier (OVA) molecule. The plaque-forming cell (PFC) response generated in the presence of cloned Th cells is idiotypically diverse with 5-40% of the secreting B cells bearing the TEPC-15 (T15) idiotype. The interaction of the cloned Th cells and unprimed B cells requires recognition of B cell surface Ia glycoproteins for all B cells activated to secrete anti-PC antibody, whether they be T15-bearing or not. More importantly, however, effective interaction between a cloned Th cell and a B cell is determined by the quantity of B cell surface Ia glycoproteins. Our results indicate that quantitative differences in B cell surface Ia antigens are directly related to B cell activation by the cloned Th cell. The high Ia density B cells are most easily activated by cloned Th cells, and these appear to be mainly non-T15-bearing. These data suggest that the failure of cloned Th cells to effectively activate T15-bearing B cells in vitro may be due to the lower relative Ia density of these B cells and therefore to their inability to interact effectively with cloned Ia-recognizing Th cells. These results imply that monoclonal T cells may distinguish between T15-bearing and non-T15-bearing B cells based on their Ia density.

Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1699-1705 ◽  
Author(s):  
Yoshinori Nagai ◽  
Rintaro Shimazu ◽  
Hirotaka Ogata ◽  
Sachiko Akashi ◽  
Katsuko Sudo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Structural Similarity ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Cell Surface Molecule

RP105 is a B-cell surface molecule that has been recently assigned as CD180. RP105 ligation with an antibody induces B-cell activation in humans and mice, leading to proliferation and up-regulation of a costimulatory molecule, B7.2/CD86. RP105 is associated with an extracellular molecule, MD-1. RP105/MD-1 has structural similarity to Toll-like receptor 4 (TLR4)/MD-2. TLR4 signals a membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS). MD-2 is indispensable for TLR4-dependent LPS responses because cells expressing TLR4/MD-2, but not TLR4 alone, respond to LPS. RP105 also has a role in LPS responses because B cells lacking RP105 show hyporesponsiveness to LPS. Little is known, however, regarding whether MD-1 is important for RP105-dependent LPS responses, as MD-2 is for TLR4. To address the issue, we developed mice lacking MD-1 and generated monoclonal antibodies (mAbs) to the protein. MD-1–null mice showed impairment in LPS-induced B-cell proliferation, antibody production, and B7.2/CD86 up-regulation. These phenotypes are similar to those of RP105-null mice. The similarity was attributed to the absence of cell surface RP105 on MD-1–null B cells. MD-1 is indispensable for cell surface expression of RP105. A role for MD-1 in LPS responses was further studied with anti–mouse MD-1 mAbs. In contrast to highly mitogenic anti-RP105 mAbs, the mAbs to MD-1 were not mitogenic but antagonistic on LPS-induced B-cell proliferation and on B7.2 up-regulation. Collectively, MD-1 is important for RP105 with respect to B-cell surface expression and LPS recognition and signaling.

scholarly journals The Mycoplasma-Derived Macrophage-Activating 2-Kilodalton Lipopeptide Triggers Global Immune Activation on Nasal Mucosa-Associated Lymphoid Tissues

2004 ◽  
Vol 72 (12) ◽  
pp. 6978-6986 ◽  
Author(s):  
Faiza Rharbaoui ◽  
Astrid Westendorf ◽  
Claudia Link ◽  
Sandra Felk ◽  
Jan Buer ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nasal Mucosa ◽  
Cell Activation ◽  
Pcr Analysis ◽  
Lymphoid Tissues ◽  
Tlr2 Expression ◽  
Activation Markers ◽  
Regulated Expression

ABSTRACT A better knowledge on how immune responses are initiated in mucosal tissues would facilitate the design of new mucosal vaccines, as well as improve our understanding on host defense against infection. We investigated the mechanisms of adjuvanticity of the Mycoplasma-derived macrophage-activating 2-kDa lipopeptide (MALP-2), which binds to the heterodimer formed by the Toll-like receptors 2 and 6 (TLR2 and -6), at the level of the murine nasal mucosa-associated lymphoid tissues (NALT). TLR2 expression analysis demonstrated that several cell types from the nasal cavity were able to overexpress this receptor, either constitutively (such as B cells) or after stimulation (i.e., T cells). MALP-2 stimulated a strong B-cell activation. In addition, the antigen presentation capacity of dendritic cells was improved after in vivo loading with antigen in the presence of MALP-2. We also observed an up-regulated expression of activation markers and adhesion molecules on T cells, suggesting that they have enhanced responsiveness and interaction potential. Quantitative reverse transcription-PCR analysis showed that MALP-2 administration resulted in the stimulation of a proinflammatory cascade. We observed an early up-regulated expression of IP-10, MCP-1, MCP-3, MIP-1α, MIP-2, and CCR-2 which was reversed within 36 h. The obtained results demonstrated that MALP-2 creates a reversible local microenvironment which promotes effective priming of T and B cells in the NALT.

scholarly journals Humans with chronic granulomatous disease maintain humoral immunologic memory despite low frequencies of circulating memory B cells

Blood ◽  
2012 ◽  
Vol 120 (24) ◽  
pp. 4850-4858 ◽  
Author(s):  
Susan Moir ◽  
Suk See De Ravin ◽  
Brian H. Santich ◽  
Jin Young Kim ◽  
Jacqueline G. Posada ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Chronic Granulomatous Disease ◽  
Somatic Hypermutation ◽  
Memory B Cells ◽  
Potential Contribution ◽  
Granulomatous Disease ◽  
Immunologic Memory ◽  
Activation Markers ◽  
Specific Memory

Abstract CD27+ memory B cells are reduced in the blood of patients with chronic granulomatous disease (CGD) for reasons and consequences that remain unclear. Here we confirm not only decreased CD27+ but also IgG+ B cells in the blood of CGD patients compared with healthy donors (HDs). However, among IgG+ B cells, the ratio of CD27− to CD27+ was significantly higher in CGD patients compared with HDs. Similar to conventional memory B cells, CD27−IgG+ B cells of CGD patients expressed activation markers and had undergone somatic hypermutation, albeit at levels lower than their CD27+ counterparts. Functional analyses revealed slight reductions in frequencies of total IgG but not influenza-specific memory B-cell responses, as measured by Elispot in CGD patients compared with HDs. Serum IgG levels and influenza-specific antibodies were also normal in these CGD patients. Finally, we provide evidence that influenza-specific memory B cells can be present within the CD27−IgG+ B-cell compartment. Together, these findings show that, despite reduced circulating CD27+ memory B cells, CGD patients maintain an intact humoral immunologic memory, with potential contribution from CD27− B cells.

scholarly journals Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Silvia Portugal ◽  
Christopher M Tipton ◽  
Haewon Sohn ◽  
Younoussou Kone ◽  
Jing Wang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Viral Infections ◽  
Somatic Hypermutation ◽  
Plasmodium Falciparum Malaria ◽  
Cell Receptor ◽  
Memory B Cells ◽  
B Cell Receptor ◽  
Chronic Infections ◽  
Malaria Exposure

Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic malaria exposure is associated with a large increase in atypical memory B cells (MBCs) that resemble B cells expanded in a variety of persistent viral infections. Understanding the function of atypical MBCs and their relationship to classical MBCs will be critical to developing effective vaccines for malaria and other chronic infections. We show that VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable indicating a common developmental history. Atypical MBCs express an array of inhibitory receptors and B cell receptor (BCR) signaling is stunted in atypical MBCs resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion. Thus, in response to chronic malaria exposure, atypical MBCs appear to differentiate from classical MBCs becoming refractory to BCR-mediated activation and potentially interfering with the acquisition of malaria immunity.

RP105 Is Associated With MD-1 and Transmits an Activation Signal in Human B Cells

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2815-2822 ◽  
Author(s):  
Yoshihiro Miura ◽  
Rintaro Shimazu ◽  
Kensuke Miyake ◽  
Sachiko Akashi ◽  
Hirotaka Ogata ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
B Cell Activation ◽  
Cell Surface Molecule ◽  
Induced Apoptosis

Abstract RP105 was originally discovered as a mouse B-cell surface molecule that transmits an activation signal. The signal leads to resistance against irradiation-induced apoptosis and massive B-cell proliferation. Recently, we found that mouse RP105 is associated with another molecule, MD-1. We have isolated here the human MD-1 cDNA. We show that human MD-1 is also associated with human RP105 and has an important role in cell surface expression of RP105. We also describe a monoclonal antibody (MoAb) that recognizes human RP105. Expression of RP105 is restricted to CD19+ B cells. Histological studies showed that RP105 is expressed mainly on mature B cells in mantle zones. Germinal center cells are either dull or negative. RP105 is thus a novel human B-cell marker that is preferentially expressed on mature B cells. Moreover, the anti-RP105 MoAb activates B cells, leading to increases in cell size, expression of a costimulatory molecule CD80, and DNA synthesis. The B-cell activation pathway using RP105 is conserved in humans. © 1998 by The American Society of Hematology.

scholarly journals Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells

2019 ◽  
Vol 216 (9) ◽  
pp. 2071-2090 ◽  
Author(s):  
Thomas Liechti ◽  
Claus Kadelka ◽  
Dominique L. Braun ◽  
Herbert Kuster ◽  
Jürg Böni ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Chemokine Receptors ◽  
Marginal Zone ◽  
Cell Receptor ◽  
Activation Markers ◽  
Marginal Zone B Cells ◽  
Cell Responses ◽  
Functional Capacities ◽  
Hiv 1

Perturbations in B cells are a hallmark of HIV-1 infection. This is signified by increased numbers of exhausted CD21neg memory B cells, driven by continuous antigen-specific and bystander activation. Using high-dimensional flow cytometry, we demonstrate that this exhausted phenotype is also prevalent among peripheral antigen-inexperienced naive and marginal zone (MZ) B cells in acute and chronic HIV-1 infection. A substantial fraction of naive and MZ B cells exhibit down-regulated CD21 levels and diminished response to B cell receptor (BCR)–dependent stimulation. Compared with CD21pos subsets, the CD21neg naive and MZ B cells differ in the expression of chemokine receptors and activation markers. Effective antiretroviral treatment normalizes peripheral naive and MZ B cell populations. Our results emphasize a more widely spread impairment of B cells in HIV-1 infection than previously appreciated, including antigen-inexperienced cells. This highlights the importance of monitoring functional capacities of naive B cells in HIV-1 infection, as exhausted CD21neg naive B cells may severely impair induction of novel B cell responses.

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